Sustained release matrix tablet of 100 mg losartan potassium: Formulation development and in vitro characterization

Abstract Sustained release matrix tablets of 100 mg losartan potassium HCl were fabricated with two release retarding polymers namely HPMC K100 M and affinisol by direct compression method. Nine trial formulations were prepared by varying content of these polymers, each from 50 mg to 100 mg; keeping the total weight of the tablet 310 mg. The best formulation was selected based on in vitro drug release profile for 12 hours conducted in Type II dissolution apparatus at 50 rpm and water as dissolution medium. Pre-compression parameters such as bulk density, tap density, Carr's index and Hausner ratio were evaluated for the selected tablet. The tablets were subjected to thickness, weight variation test, drug content, hardness and friability. Drug release kinetics, surface morphology and accelerated stability study were investigated for that selected formulation. Formulation F4 with the composition of 75 mg HPMC K100M and 100 mg affinisol was selected as the best formulation that extended the drug release up to 12 hours. Pre-compression parameters and other tableting properties were within the Pharmacopoeia limit. Release kinetics analysis proved non-fickian zero-order drug release and that was further confirmed by surface morphology of the tablets before and after dissolution study visualized by SEM. The developed formulation was found to be stable for one month stored at 60 ○C.

Development And Evaluation Of Lamivudine Sustained Release Matrix Tablets

Lamivudine is approved for clinical use and used widely in treatment of Hepatitis Band AIDS either alone or in combination with another antiviral drugs because of its watersolubility and shorter half-life (5-7 hrs) drug requires frequent dosing by oral route, off variousrecent techniques for controlling drug release, matrix system offer various advantages of easeof formulation better control on release profile of drug and better patient compliance. Thematrix tablets formulation by direct compression method is most acceptable in large scaleproduction. It is concluded that formulation of sustained release tablet of Lamivudinecontaining 80 mg of hydroxypropyl-methylcellulose E15 (high viscosity grade) and 80 mg ofethylcellulose i.e. formulation F7 can be taken as an ideal or optimized formulation ofsustained release tablets for 16 hours release as it fulfills all the requirements for sustainedrelease tablet and our study encourages for the further clinical trials and long term stabilitystudy on this formulation.

Formulation And Evaluation Of Garlic Powder Loaded Floating Matrix Tablet

Objective: The objective of the present work was to formulate and evaluate a stable, odour free garlic powder loaded floating matrix tablet for the treatment of peptic ulcers. Methods: A gastro-retentive floating matrix tablet (FMT) formulation of garlic powder (GP) was prepared using various concentrations of hydroxypropyl methylcellulose K4M (HPMC K4 M) and effervescent system (sodium bicarbonate and citric acid in 1:1 % w/w) to achieve desirable floating time (FT), floating lag time (FLT) and drug release. Wet granulation method was selected using ethanol as a binder for preparation of tablet. 32 full factorial designs were used for selection of suitable polymer concentration and effervescent system. Nonenteric film coating was applied to mask GP odour. Results: It was observed that FMT with optimum quantities of HPMC K4M and the effervescent system showed 97 % of drug release in 12 h with FT up to 10 h and minimum FLT of 3 min. There was no significant change in FLT, FT and drug content during the stability study of FMT. Conclusion: A stable, sustained release FMT of GP tablets using HPMC K4M and an effervescent system was successfully prepared. This formulation can overcome problems of taste and odour masking, gastric irritation, and loss of active constituents present in garlic.

Estimation Of Bacoside-A In Bacopa Monnieri Aerial Parts Using Tlc Densitometry

Objective: The objective of the present work was to formulate and evaluate a stable, odour free garlic powder loaded floating matrix tablet for the treatment of peptic ulcers. Methods: A gastro-retentive floating matrix tablet (FMT) formulation of garlic powder (GP) was prepared using various concentrations of hydroxypropyl methylcellulose K4M (HPMC K4 M) and effervescent system (sodium bicarbonate and citric acid in 1:1 % w/w) to achieve desirable floating time (FT), floating lag time (FLT) and drug release. Wet granulation method was selected using ethanol as a binder for preparation of tablet. 32 full factorial designs were used for selection of suitable polymer concentration and effervescent system. Nonenteric film coating was applied to mask GP odour. Results: It was observed that FMT with optimum quantities of HPMC K4M and the effervescent system showed 97 % of drug release in 12 h with FT up to 10 h and minimum FLT of 3 min. There was no significant change in FLT, FT and drug content during the stability study of FMT. Conclusion: A stable, sustained release FMT of GP tablets using HPMC K4M and an effervescent system was successfully prepared. This formulation can overcome problems of taste and odour masking, gastric irritation, and loss of active constituents present in garlic.

Non-Starch Plant Polysaccharides: Physicochemical Modifications and Pharmaceutical Applications.

Polysaccharides of natural, synthetic or semi-synthetic origin have been used from time immemorial in the development of drug delivery systems designed to achieve tailored and site-specific drug release. Starch-based polysaccharides derived from plants have been extensively studied in this regard. Natural polymeric excipients are preferred over their synthetic counterparts owing to their low cost, availability, biocompatibility, biodegradability and non-toxicity. The present review attempts to provide a new direction and a comprehensive insight on the physical properties, rheological behavior, toxicity profile, pharmaceutical applications, swelling behavior and drug diffusion kinetics from dosage forms based on non-starch polysaccharides of plant origin such as, psyllium, pectin, arabinoxylan, xyloglucan, guar gum galactomannan and konjac glucomannan. It has been observed from the current review that non-starch polysaccharides are safe for human consumption and can be successfully employed to deliver drugs specifically to stomach and colon in a sustained fashion. They have thus widened the scope of natural polymeric excipients and demand better industrial utilization on a commercial scale to minimize cost of production and to satisfy therapeutic needs in safe and effective manner.

Formulation and evaluation of lamivudine sustained release tablet using okra mucilage.

The present study was to extract the mucilage from the Okra plant (Abelmoschus esculentus) and to study the effect of mucilage concentration on in vitro release of Lamivudine from it’s sustained release matrix tablets. Mucilage was extracted from the fruits of Abelmoschus esclentus using organic solvent Acetone. The extracted mucilage was subjected to various physiological properties for its suitability as an excipient in the preparation of tablet. Lamivudine sustained release tablets were prepared using different concentration of Okra mucilage as a sustained release matrix excipient. The formulated tablets were evaluated for post compression parameters such as weight variation, hardness, friability, wetting time, water absorption ratio, and in vitro drug release studies. Stability studies of optimized formulation were carried out for three months. The results of in vitro release revealed that the release rate decreased with increase in the concentration of mucilage. The release kinetics indicated that the nature of drug release from the matrix tablets was dependent on drug diffusion and polymer relaxation and therefore followed non-fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The Okra mucilage showed promising results in terms of sustaining the release behavior of Lamivudine from the matrix. The developed sustained release tablets of Lamivudine, with extension of release up to 12 hours, can overcome all the disadvantages of conventional Lamivudine tablets.

The swelling behavior of choline fenofibrate hydrogel matrix tablets using dynamic image analysis / 药学学报

The purpose of this study is to investigate the effects of formulation on the swelling behavior of choline fenofibrate hydrogel matrix tablets and reveal the relation between swelling property and release profile using dynamic image analysis. The volume swelling ratio (SR) and height/width (k) could evaluate the swelling behavior of matrix tablets well. The mount of hydroxypropyl methylcellulose (HPMC) and the ratio between K15M and K4M affected the volume swelling ratio, while PVP didn't. The three factors all impacted k, which was an indicator of the strength of the gel formed by HPMC. The accumulative release ratio and SR, the rate of swelling and the rate of release were compared. The proper model equations were established for the results with an excellent correlation. The results prove that there is a strong relevance between the swelling behavior and release property. This study provides a guideline in the study design for hydrogel matrix tablets.

Study on Formulation Optimization of Nicorandil Sustained-release Matrix Tablet and Drug Release in vitro / 中国药房

OBJECTIVE:To optimize the formulation optimization of Nicorandil sustained-release matrix tablet,and evaluate its drug release properties in vitro. METHODS:Based on single factor test,powder direct compression method was used,using nicorandil cumulative release rate (Q) in 1,4,8,12 h as evaluation indexes,central composite design-response surface method was adopted to optimize the amount of hydroxypropyl methylcellulose(HPMC)and ethyl cellulose(EC);Q values within 12 h in different pH (1.0,5.0,6.8,7.4) media were compared. RESULTS:The optimized formulation (every tablet) was nicorandil 10 mg,HPMC 150 mg,EC 90 mg,microcrystalline cellulose 80 mg,lactose 60 mg,magnesium stearate 2%. Q1 h,Q4 h,Q8 h and Q12 h of the obtained formulation were 23.6%,51.3%,83.7% and 96.9%,respectively;deviation from the predicted values were 2.1%,1.6%,1.0%,0.2%. Q values were similar in pH 1.0-7.4 at different time points. CONCLUSIONS:The obtained Nicor-andil sustained-release matrix tablet by optimal formulation shows sustained-release effect,and the change of pH 1.0-7.4 has no in-terference in the release characteristics of main drug.

Preparation of Metformin Hydrochloride Extended Release Matrix Tablets by Direct Compression Method and Its In vitro Evaluation.

Aims: Metformin Hydrochloride, a biguanide, is an orally active antihyperglycemic agent, used in the treatment of non-insulin dependent diabetes mellitus (NIDDM). It has relatively short plasma half life, low absolute bioavailability. Extended release formulation of Metformin Hydrochloride by direct compression method has significant challenges due to its poor inherent compressibility and high dose. The aim of this study was to develop extended release tablets of Metformin Hydrochloride by direct compression method and In vitro evaluation. Study Design: Nine different formulations were made by varying drug-polymer ratio and were subjected to different physical property tests of the powder blend as well as prepared tablets, followed by dissolution test. Place and Duration of Study: Department of Pharmacy, State University of Bangladesh, Dhaka, Bangladesh, between January 2013 and July 2013. Methodology: Nine formulations of Metformin Hydrochloride matrix tablets - F-1, F-2, F- 3, F-4, F-5, F-6, F-7, F-8 and F-9 - were prepared by direct compression method using release retarding materials, Methocel K100 MCR Premium (derivative of hydroxypropyl methylcellulose - HPMC) and Xanthan gum. The drug and polymer ratio were 1:0.41, 1:0.45, 1:0.49, 1:0.59, 1:0.63, 1:0.67, 1:0.77, 1:0.81 & 1:0.85 respectively. The micromeritic behavior of the powder blends were evaluated for bulk density, angle of repose, compressibility index along with post compressional attributes of the tablets such as thickness, hardness, friability, weight variation and content of Metformin Hydrochloride in the tablets. The in-vitro drug release study was carried out in 1000 mL phosphate buffer medium (pH 6.8) at 37±0.5°C at 100 rpm for 10 hours using USP Apparatus Type-II (paddle) method. Results: FT-IR study showed drug-excipient compatibility and DSC analysis showed no solid state interaction between components. The physical properties of the powder blend and the tablets were within the acceptable limits. Maximum and minimum drug release were found in formulation F-1 and F-9 respectively which indicate that release rate is inversely proportional to the concentration of Methocel K100 MCR Premium and Xanthan gum in combination. Dissolution study also showed that, formulations F-7, F-8 & F-9 do not comply with drug release specification of USP and among the rest six formulations F- 3, F-4 & F-5 comply better with drug release specification of USP. After fitting the data to Korsmeyer-Peppas equation we found that diffusion along with erosion could be the mechanism of drug release.Considering the micromeritic behaviour of the powder blend, physical attributes of the compressed tablets, and dissolution, formulation F-4 seemed most suitable. Conclusion: Extended release Metformin Hydrochloride tablets can be produced to overcome frequent dosing related problems. However, Further study on formulation optimization and scale up, stability and bioequivalence is needed to confirm the appropriateness of these formulated extended release tablets.

Formulation and in vitro evaluation of nevirapine extended release matrix tablets.

Objective: Nevirapine (NVP) is a non nucleoside reverse transcriptase inhibitor widely used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus disease. The present study was aimed to develop generic formulation of extended release (ER) tablets of Nevirapine anhydrous (NVP) using hydrophilic polymer. Method: Nevirapine NVP(ER) tablets were prepared by different manufacturing technology i.e. direct compression, roller compaction, and wet granulation method by employing hydrophilic polymer (HPMC K15M).The matrix granules were prepared by mixing drug along with polymer and diluents in different polymer ratio from wet granulation technology used water as a granulating fluid. Results: The prepared granules were evaluated for various physicochemical parameters by official procedure and compressed in tablets. The In-vitro release profile of various batches was prepared by different technologies and has been compared with the innovator product. In-vitro release profiles of NVP from ER tablets were determined using USP apparatus type II (Paddle), 50 rpm and bath temperature 37ºC. Dissolution of tablets was carried out in 900 ml of media (phosphate buffer pH 6.8). Samples were withdrawn at predetermined time intervals up to 24 hrs and analyzed using UV detector at a wavelength of 247 nm. Conclusion: Stress stability studies indicated that the formulation is stable and In-vitro release profile study showed that formulation using wet granulation technology.

Formulation and Evaluation of sustained release matrix tablets of Glipizide.

The aim of present investigation was to enhance the solubility of glipizide (BCS Class II). Glipizide is an oral antidiabetic agent with relatively short elimination half life. Inclusion complex of Glipizide with -cyclodextrin was prepared by kneading method and evaluated for its in-vitro release. Phase solubility studies were performed according to method reported by Higuchi and Connors which was classified as AL type characterized by apparent 1:1 stability constant. The Glipizide & Beta Cyclodextrin found to be compatible which was observed from FTIR spectra of Glipizide - CD Complex. The dissolution study of Glipizide - CD complex shows significant increase in the drug release than pure drug. Matrix Glipizide - CD complex tablet complex equivalent to 10 mg Glipizide were prepared by using Hydroxy propyl methyl cellulose (HPMC), Carboxy methyl cellulose sodium (NaCMC) and Microcrytalline cellulose (MCC). The tablets were evaluated for various tests like hardness, friability, disintegration and in-vitro dissolution studies.

Design and Development of Atenolol Matrix Tablet Employing Natural and Synthetic Polymers.

The main objective of the present work was to develop sustained release matrix tablets of Atenolol. To reduce the frequency of administration and to improve the patient compliance, a once daily sustained release formulation of Atenolol is desirable. So sustained release Matrix Tablet of Atenolol was designed by using different polymers viz.Starch, Xanthan Gum, Vee Gum , Guar Gum, Gum Accacia, Tragacanth, Hupu Gum were used as natural polymers and Eudragit-L100, Ethyl Cellulose, Sodium Carboxy Methyl Cellulose (Na-CMC) ,Hydroxy Propyl Methyl Cellulose (HPMC) (5&15cps), Methyl Cellulose, Kollidon were used as synthetic polymers. After fixing the ratio of drug and polymer for control the release of drug up to desired time, the release rates were modulated by Single polymer, combination of two different rates controlling material. The FT-IR study revealed that there was no chemical interaction between drug and excipients. The granules were prepared by dry granulation method. Precompressional parameters i.e. angle of repose, percent compressibility, and Hausner’s ratios were studied. These results indicate that granules are good flowing characteristics. After evaluation of physical properties like Weight variation, Hardness, Thickness, Friability of tablet, the different formulations checked for the Percentage Drug content which having good uniformity. The results of drug dissolution studies showed improved drug release, retardation effects of the polymers and could achieve better performance. After eight hours dissolution test, dissolution profiles showed that better sustained release was observed from starch and veegum containing formulation and eudragit and ethyl cellulose containing formulation of atenolol matrix tablet. It was also observed that the presence of starch caused an increase in the release rate of atenolol matrix tablet. The present study shows a relatively simple method to design and develop Atenolol matrix tablet.

An Overview: Matrix Tablet as Controlled Drug Delivery System.

In past decade great interest got generated on replacing conventional administration of drug by delivery system which would release effective quantities from a protected supply at a controlled rate over a long period of time. An appropriately designated controlled release drug delivery system can be are major advance toward solving problems concerning targeting of a drug to a specific organ or a tissue and controlling the rate of a drug delivery to the target site. Matrix system are favoured because of their simplicity, patient compliance etc, than traditional drug delivery(TDS) which have many drawbacks like repeated administration, fluctuation in blood concentration level etc. Developing oral sustained release matrix tablet with constant release rate has always been a challenge to the pharmaceutical technologist. Most of drugs, if not formulated properly, may readily release the drug at a faster rate, and are likely to produce toxic concentration of the drug on oral administration. Hydrophilic polymers have become product of choice as an important ingredient for formulating sustained release formulations.

Formulation and In-Vitro Characterization of Acyclovir Floating Matrix Tablets: A Factorial Design Study.

The objective of present study was to develop controlled release floating matrix tablets of Acyclovir using combination of release retarding polymers: hydroxypropyl methylcellulose (HPMC K15M CR) and polyethylene oxide (Polyox WSR 303) for treatment of herpes infections using direct compression technique. The influence of type of polymer and its concentration on the drug release from prepared floating tablets was investigated using a 32 factorial design. Independent variables selected were concentration of Polyox WSR 303 (X1) and HPMC K15M CR (X2) while dependent variables were percentage cumulative drug release at 3, 9 and 12 h (Q3, Q9, and Q12). Analysis of variance (ANOVA) and multiple regression analysis showed significant effect on Q3, Q9, and Q12. Formulations also contained sodium bicarbonate (NaHCO3) and anhydrous citric acid as floating agent, polyvinyl pyrrolidone (PVP K30) as dry binder and microcrystalline cellulose (MCC, Avicel PH 102) as diluent. The floating tablets were evaluated for their floating lag time (FLT), floating duration, hardness, friability, weight variation, and in-vitro drug release, dissolution efficiency and accelerated stability study. F2 with Polyox WSR 303 (50 mg) and HPMC K15M CR (15 mg) gave best results. Stability study revealed optimized formulation F2 to remain stable. A controlled release floating matrix tablet of Acyclovir was successfully prepared by using Polyox WSR 303 and HPMC K15M CR.

Formulation and evaluation of colon targeted drug delivery system of levetiracetam using pectin as polymeric carrier.

The aim of the present work was to develop and evaluate colon specific sustained release tablet using levetiracetam (LEV), microbially degradable polymeric carrier (pectin), coating material and matrix forming polymers. The colon targeted tablet was prepared by wet granulation technique using different percentage of pectin as matrix carrier, starch mucilage as a binding agent, HPMC K-100 as swellable polymer and coated with Eudragit polymers. Pectin, drug and physical mixture were evaluated for incompatibility study by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). All the batches of matrix tablet (F1-F4) were subjected for in-vitro dissolution in various simulated gastric fluids for suitability for colon specific drug delivery system. Tablets were evaluated for micromeritic properties of granules, physical properties, drug content, water uptake and erosion characteristics. F2 was optimized and subjected to coating based on evaluation results. The dissolution study of F2 revealed, in simulated intestinal fluid (SIF) release was 40.48% at the end of 6h and in simulated colonic fluids (rat caecal content) was 102.88% after degradation at the end of 8h. The colon targeted matrix tablet of LEV showed no change either in physical appearance, drug content or dissolution pattern after performing stability study for 3 months. The studies confirmed that, the designed formulation could be used potentially for colon delivery by controlling drug release in stomach and the small intestine.

Formulation and Evaluation of Bi-layered Sustained Release Matrix Tablets of Tramadol Hydrochloride.

Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique incorporating an immediate release layer and a sustained release layer. An immediate release layer was successfully designed to release the bolus dose instantaneously. Water soluble Xanthan gum, water insoluble Kollidon SR and Eudragit L 100 were used as carriers in the sustained release layer of the matrix tablet. All the tablets were evaluated for thickness, diameter, weight variation, hardness and friability. The in vitro drug release was studied for eight hour, first two hours dissolution in acidic medium followed by six hour dissolution in buffer medium. Matrix tablet showed a sustained release rate with a controlled fashion as a function of the quantity of polymer used. The in vitro drug release data were fitted with several mathematical models and mean dissolution time along with fractional dissolution time values (T25%, T50% and T80%) were calculated. Xanthan gum was found to be the most effective rate retarding agent compared to Kollidon SR and Eudragit L 100, when used at same ratio in the formulations.

In Vitro Evaluation of Oral Extended Release Drug Delivery System for Metoprolol Succinate Using Kollidon SR.

The objective of this study was to develop a sustained release matrix tablet Metoprolol Succinate by cost saving and production efficient process. Among various tablet manufacturing process, direct compression is the simplest and cost saving process. Different trials were formulated and evaluated using different concentrations of directly compressible grade Kollidon SR as release retardant. The formulated tablets were evaluated for physical and dissolution study using buffer medium. The most outstanding aspect of this study is to monitor the influence of different percentage of Kollidon SR on release rate from the matrix tablet. In this study, influence of different ratio of polymer concentration on drug release was evaluated. The release pattern of different batches were evaluated for Zero order, Higuchi, First order, Krosmeyer-Peppas and Hixson-Crowell kinetics and showed that all the batches followed best the Higuchi kinetics. The drug release kinetics was found to be governed by the amount of the polymer in the matrix system. The higher polymeric content in the matrix decrease the release rate of the drug. The nature of the drug release from the matrix tablets was dependent on drug diffusion and polymer relaxation and therefore followed non-Fickian or anomales release. The studies indicated that the drug release can be modulated by varying the concentration of the polymer. Among the four formulations, formulation 1 is the best formulation as it controls the release best and best linearity for zero order plots.

Development of pH-independent matrix type sustained release drug delivery system of propranolol hydrochloride.

The characteristics of a new Polyvinylacetate/Povidone based excipient, Kollidon® SR were evaluated for application in extended release matrix tablets. The effects of the following formulation and process variables on tablet properties and drug release were tested: Kollidon® SR concentration in the tablet, addition of external binder for wet granulation, presence of an enteric polymer in the matrix, method of manufacturing and compression force. The similarities in release profiles were evaluated by applying the model independent f2 similarity factor. It was found that Kollidon® SR is suitable for pH-independent extended release matrix tablets. A minimum concentration of 30% polymer was necessary to achieve a coherent matrix, able to extend the release of the incorporated drugs. Increasing the Kollidon® SR concentration in the tablet led to a slower drug release. Drug release followed square root of time dependent kinetics, thus indicating a diffusion-controlled release mechanism. The drug release was influenced by the aqueous solubility of the drug. The drug release rate was faster for wet granulation than direct compression, thus making direct compression the method of choice for manufacturing Kollidon® SR extended release systems. It was found that Kollidon® SR was the main release controlling agent in the presence of an external binder or enteric polymer in the matrix. A significant reduction in the dissolution rates associated with an increase in tablet hardness was observed during the stability test under accelerated conditions. The developed propranolol matrix tablets formulation was compared to the reference listed product (Inderal® LA capsules). It was concluded that Kollidon® SR is a potentially useful excipient for the production of pH-independent extended release matrix tablets.

Formulation and Evaluation of Sustained Release Matrix Tablets of Metformin Hydrochloride Using pH Dependent and pH Independent Methacrylate Polymers.

Metformin hydrochloride is recommended globally as first line therapy due to its favorable profile on morbidity and mortality associated with type-2 diabetes mellitus. However, limitations of multiple dosing and risk of triggering gastrointestinal symptoms make its dose optimization difficult. Extended-release metformin matrix tablets were prepared by direct compression of drug and different pH-dependent (Eudragit L-100 and S-100) and pH-independent (Eudragit RLPO and RSPO) polymer combinations. The influence of varying the polymer/polymer (w/w) ratio was evaluated. Among the different examined polymer blends, matrix tablets based on S-100/RLPO and S-100/RSPO mixtures gave the more sustained release pattern. The excipients used in this study did not alter physicochemical properties of the drug, as tested by Fourier transform Infrared Spectroscopy and the thermal analysis using differential scanning calorimetry. All the batches were evaluated for thickness, weight variation, hardness, and drug content uniformity. The in vitro drug dissolution study was carried out using USP 22 apparatus II, paddle method and the release mechanisms were explored. Mean dissolution time is used to characterize drug release rate from a dosage form and indicates the drug release retarding efficiency of polymer. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled to anomalous type. Fitting the data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release.

Correlação in vitro-in vivo para formas farmacêuticas sólidas de liberação modificada contendo diclofenaco de sódio / In vitro-in vivo correlation for sodium diclofenac modified release tablet formulations

A correlação in vitro-in vivo (CIVIV) refere-se ao estabelecimento de uma relação racional entre as propriedades biológicas, ou parâmetros derivados destas, produzidos por uma forma farmacêutica e suas propriedades ou características físico-químicas. O estabelecimento desse tipo de correlação de dados pode possibilitar a substituição dos estudos in vivo, necessários à demonstração da bioequivalência, pelos estudos in vitro, no caso de alterações no processo de fabricação pós-registro. Os sistemas matriciais apresentam, como principal exemplo de material controlador da liberação, substâncias poliméricas formadoras de matrizes hidrofílicas. Hidroxipropilmetilcelulose (HPMC) é um excipiente de escolha para o preparo de matrizes hidrofílicas, devido à capacidade de formação de gel e controle da liberação. O diclofenaco de sódio (DCL) é um antiinflamatório não esteroidal com ação analgésica e antipirética. Considerando suas características físico-químicas e farmacológicas, é objetivo deste trabalho o estabelecimento de uma CIVIV para DCL incorporado em sistemas matriciais. Os comprimidos de DCL com HPMC foram desenvolvidos e submetidos aos ensaios de dissolução utilizando os aparatos 1, 2, 3 e 4 conforme as especificações farmacopeicas. Foi realizado o estudo de biodisponibilidade, seguindo as normas éticas, com as formulações selecionadas. A partir dos dados de absorção obtidos pela técnica de deconvolução e dos dados de dissolução foi estabelecida a correlação. Os resultados demonstraram que o aumento da concentração de HPMC produziu a redução da velocidade de dissolução e, dependendo da condição de estudo, estas diferenças foram mais ou menos significativas. Os comprimidos com concentração intermediária de HPMC (15 a 20%) foram mais sensíveis às alterações de formulação e das condições do ensaio de dissolução. As formulações contendo 30% de HPMC praticamente não modificaram o perfil de dissolução, mesmo com alterações na formulação e condições de estudo. No...

The term in vitro-in vivo correlation (IVIVC) refers to the establishment of a rational relationship between the biological properties, or a parameter derived from a biological property produced by a dosage form, and a physicochemical characteristic or property of the same dosage form. The establishment of IVIVC enables the substitution of in vivo studies for in vitro studies to evaluate bioequivalence, e.g. in case of post-approval changes. Matrix tablets employ mainly hydrophilic polymers to control drug release. Hydroxypropylmethylcellulose (HPMC) is an excipient of choice for preparation of hydrophilic matrices, due to its gel formation and controlled drug release capacities. Sodium diclofenac (SD) is a non-steroidal anti-inflammatory drug with analgesic and antipyretic effects. Considering its physicochemical and pharmacological characteristics, the objective of this work is to establish an IVIVC for HPMC matrix tablets containing SD. HPMC matrix tablets with SD were formulated and submitted to dissolution testing using apparatus 1, 2, 3 and 4 in accordance with pharmacopoeial specifications. The bioavailability study was carried out under ethical guidelines, using the selected formulations. The correlation was obtained by plotting absorption data, obtained from diclofenac plasmatic curves through a deconvolution technique, against dissolution data. The results showed that the increase of HPMC concentration produces a decrease of the drug dissolution rate and these differences were more or less significant, depending on the study conditions. Tablets with intermediate HPMC concentrations (15 to 20%) were more sensitive to changes in dissolution conditions. Formulations containing 30% HPMC do not present changes in dissolution profiles, even when the formulation or the study conditions change. Formulations F1, F2A, F3 and Voltaren® 50 mg as reference product were used in the bioavailability study to establish IVIVC. The linear correlation between...